Influência do Receptor B1 de Cininas na Fisiopatologia da Obesidade e do Diabetes Mellitus em Camundongos ob/ob

Abstract

The kallikrein-kinin system (KKS) is involved in many biological processes such as modulating pain, vasodilation, vascular permeability, edema and inflammation, with effects mediated by two specific receptors coupled to G protein, B1 and B2 kinin receptor. The KKS has recently been associated with glucose homeostasis and insulin resistance. The aim of this study was to investigate the participation of B1 receptor (B1R) of kinins in the metabolic processes related to obesity and type 2 diabetes in obese mice. For this we used mice deficient for leptin and knockouts for B1R kinin (obB1). When compared, the animals obB1 showed a reduction in food intake in the whole study period (4 to 26 ° week of life); less weight gain, both at 3 months (obWT, 63.79 ± 1.59; obB1, 51.22 ± 1.09 g, p <0.001) and at 6 months of age (obWT, 74.61 ± 1, 04; obB1, 57.98 ± 1.58 g, p <0.001); and less fat deposit. In the glucose tolerance test, obB1 animals had higher glucose uptake than their controls when young (obWT, 46045 ± 3492; obB1, 30875 ± 2311 (mg / dL) .min, p <0.01). Additionally, there was an increase in liver weight in these animals, while older (obWT, 3.29 ± 0.24, 4.09 ± 0.06 g obB1, p <0.001). In conclusion, the B1R gene silencing offers a protection against obesity have a significant impact on the glucose homeostasis. These results suggest that the KKS may be a new target for the development of new pharmacologic strategies for treating metabolic diseases such as obesity and type 2 diabetes mellitus.